Preoperative Chemoradiotherapy For Rectal Cancer Research Articles

169 Nutritional Support During Preoperative Chemoradiotherapy for Rectal Cancer Prevents Significant Weight Loss

169 Nutritional Support During Preoperative Chemoradiotherapy for Rectal Cancer Prevents Significant Weight Loss

The role of lateral pelvic lymph node dissection in advanced rectal cancer: a review of current evidence and outcomes.

Metastatic lateral pelvic lymph nodes (LPNs) in rectal cancer significantly impact the prognosis and treatment strategies. Western practices emphasize neoadjuvant chemoradiotherapy (CRT), whereas Eastern approaches often rely on LPN dissection (LPND). This review examines the evolving role of LPND in the context of modern treatments, including total neoadjuvant therapy (TNT), and the impact of CRT on the management of clinically suspicious LPNs. We comprehensively reviewed the key literature comparing the outcomes of LPND versus preoperative CRT for rectal cancer, focusing on recent advancements and ongoing debates. Key studies, including the JCOG0212 trial and recent multicenter trials, were analyzed to assess the efficacy of LPND, particularly in conjunction with preoperative CRT or TNT. Current evidence indicates that LPND can reduce local recurrence rates compared to total mesorectal excision alone in patients not receiving radiation therapy. However, the benefit of LPND in the context of neoadjuvant CRT is influenced by the size and pretreatment characteristics of LPNs. While CRT can effectively control smaller metastatic LPNs, larger or clinically suspicious LPNs may require LPND for optimal outcomes. Advances in surgical techniques, such as robotic-assisted LPND, offer potential benefits but also present challenges and complications. The role of TNT in controlling metastatic LPNs and improving patient outcomes is emerging but remains underexplored. The decision to perform LPND should be individualized based on patient-specific factors, including LPN size, response to neoadjuvant treatment, and surgeon expertise. Future research should focus on optimizing treatment protocols and further evaluating the role of TNT in managing metastatic LPNs.

Clinical and pathological parameters predicting pathologic complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Objective The aim of this study is to identify possible clinical predictors of complete response after neoadjuvant treatment in locally advanced rectal cancer (LARC) patients. Background Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision and postoperative adjuvant chemotherapy for LARC is the standard of care with a local recurrence rate of only 5–10%. On the other hand, various people react differently to neoadjuvant CRT. Neoadjuvant CRT is well received by the majority of patients, with a pathologic complete response (pCR) occurring in 10–30% of cases. Predicting the response to neoadjuvant CRT is crucial from a clinical standpoint, since patients with pCR have a better prognosis and may require a different treatment plan than patients without pCR. As a result, predicting pCR following neoadjuvant CRT for rectal cancer continues to be extremely useful for treating physicians. To identify the clinical and pathological variables linked to a full response to preoperative CRT for rectal cancer, we assessed a group of patients with pCR in this study. Patients and methods The study included 153 patients with LARC that were enrolled in the study based on specific inclusion and exclusion criteria. Patients were treated by standard neoadjuvant therapy. Surgical resection was planned for 6–8 weeks after the completion of neoadjuvant CRT, irrespective of the response to CRT. Pathological examination was performed to assess pathological response in the resected specimen. pCR was defined as the absence of viable tumor cells in the surgical specimen, including lymph nodes. Results After neoadjuvant chemoradiation, the pCR rate for rectal cancer patients was 20.8%; patients were split into pCR and non-pCR groups. Age, sex, BMI, performance score, tumor stage, tumor differentiation, tumor location, and surgical method were all evenly distributed across the two groups. The results of the multivariate analysis showed that pretreatment lymph node status, tumor size, and a carcinoembryonic antigen level of less than or equal to 5 ng/ml were independent risk factors of an elevated likelihood of pCR, as was an interval of more than or equal to 8 weeks between the completion of chemoradiation and treatment. Conclusion The pCR in rectal cancer following neoadjuvant chemoradiation is predicted by pretreatment carcinoembryonic antigen level of less than or equal to 5 ng/ml, an interval of more than or equal to 8 weeks between the end of chemoradiation and surgical resection, tumor size greater than 5 cm, and pretreatment lymph node status. By utilizing these predictive variables, we are able to forecast patients’ outcomes and create flexible treatment plans. In certain, very specific situations, a wait-and-see policy might be appropriate.

Poor prognostic effects of lymphocytopenia induced by preoperative chemoradiotherapy in rectal cancer

Lymphocytopenia is a potential poor prognostic factor in various cancers. We evaluated the prognostic effect of lymphocytopenia caused by preoperative radiation therapy and chemotherapy in rectal cancer patients.

Restaging of rectal cancer with hybrid positron emission tomography magnetic resonance imaging after preoperative chemoradiotherapy.

This study determines the sensitivity and specificity of positron emission tomography/magnetic resonance imaging (PET/MRI) parameters in predicting treatment response in patients with localised rectal cancer who have undergone preoperative chemoradiotherapy (CRT). Patients with stage I-III adenocarcinoma of the rectum planned for preoperative CRT followed by surgery were recruited. Patients had PET/MRI scans at baseline and 6-8 weeks post-CRT. Functional MRI and PET parameters were assessed for their diagnostic accuracy for tumour regression grade (TRG). Nonparametric receiver operating characteristic analysis was employed to determine the area under the ROC curve (AUC), and the sensitivity and specificity of each quantile cut-off. A total of 31 patients were recruited, of whom 20 completed study protocol. All patients included had mid or lower rectal tumours. There were 16 patients (80%) with node-positive disease at presentation. The median time to surgery was 75.5 days (range 52-106 days). Histopathological assessment revealed 20% good responders (TRG 1/2), and the remaining 80% of patients had a poor response (TRG 3/4). When predicting good responders, the AUC values for percent maximum thickness reduction and percent apparent diffusion coefficient (ADC) change were 0.82 and 0.73, respectively. A maximum thickness reduction cut-off of >47% and a percent ADC change of >20% yielded a sensitivity and specificity of 75%/95% and 75%/73%, respectively. Parameters such as percent maximum thickness reduction and percent ADC change may be useful for predicting good responders in patients undergoing preoperative CRT for rectal cancer. Larger studies are warranted to establish the utility of PET/MRI in rectal cancer staging.

Efficacy of hypofractionated preoperative chemoradiotherapy in rectal cancer.

The efficacy and toxicity of hypofractionated preoperative chemoradiotherapy (HPCRT) combined with oral capecitabine was evaluated in patients with rectal cancer. HPCRT was delivered by intensity-modulated radiotherapy of either 33 Gy to the whole pelvis or 35 Gy in 10 fractions to the primary tumor and 33 Gy to the surrounding pelvis. Surgery was performed 4-8 weeks after HPCRT completion. Oral capecitabine was administered concurrently. A total of 76 patients were eligible for this study, and patient numbers in clinical stages I, II, III and IVA were 5, 29, 36 and 6, respectively. Tumor response, toxicity and survival were analyzed. A total of 9/76 patients (11.8%) achieved a pathological complete response. Sphincter preservation was achieved in 23/32 (71.9%) and 44/44 (100%) of patients with a distal extent from the anal verge of ≤5 and >5 cm, respectively. A total of 28/76 patients (36.8%) achieved tumor-downstaging and 25/76 (32.9%) achieved nodal (N)-downstaging. The 5-year disease-free survival (DFS) and overall survival rates were 76.5% and 90.6%, respectively. In the multivariate analysis for DFS, pathological N stage and lymphovascular space invasion were notable prognostic factors. A total of 6 patients in stage IVA underwent salvage treatments for lung or liver metastasis after HPCRT completion, and all 6 were alive at the last follow-up. Only 4 patients experienced grade 3 postoperative complications. No grade 4 toxicities were observed. HPCRT of 33 or 35 Gy in 10 fractions showed similar results to those of long-course fractionation. This fractionation scheme could be beneficial for patients with early stage disease, locally advanced rectal cancer, simultaneous distant metastasis requiring early intervention or for patients who wish to avoid multiple hospital visits.

Predictors and histological effects of preoperative chemoradiotherapy for rectal cancer and control of lateral lymph node metastasis

IntroductionStandard treatment strategy for low rectal cancer in Japan is different from Western countries. Total mesorectum excision (TME) + lateral lymph node dissection (LLND) is mainly carried out in Japan, whereas neoadjuvant chemoradiotherapy (nCRT) + TME is selected in Western countries. There is no clear definition of preoperative diagnosis of lateral lymph node metastasis. If we can predict lateral lymph node swelling that can be managed by nCRT from lateral lymph node swelling that require surgical resection, clinical benefit is significant. In the current study we assessed characteristics of the lateral lymph node recurrence (LLNR) and LLND that can be managed by nCRT.Patients and MethodsPatients with low rectal cancer (n = 168) underwent nCRT between 2009 and 2016. We evaluated CEA, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lateral lymph node short axis pre and post nCRT, respectively, and also evaluated tumor shrinkage rate, tumor regression grade (TRG). We evaluated the relationship between each and LLNR.ResultsLLND was not carried out all patients. Factors associated with LLNR were PLR and lymph node short axis pre and post nCRT. (p = 0.0269, 0.0278, p < 0.0001, p < 0.0001, respectively). Positive recurrence cut-off values of lateral lymph node short-axis calculated were 11.6 mm pre nCRT and 5.5 mm post nCRT.ConclusionResults suggest that PLR before and after CRT was associated with control of LLNR, and LLND should be performed on lateral lymph nodes with short-axis of 5 mm and 11 mm pre and post nCRT.

Improvement in the Assessment of Response to Preoperative Chemoradiotherapy for Rectal Cancer Using Magnetic Resonance Imaging and a Multigene Biomarker.

Simple SummaryPreoperative chemoradiotherapy is now the gold standard for treating locally advanced rectal cancer and has been demonstrated to decrease local recurrence and promote sphincter preservation. Therefore, developing methods to accurately predict patients’ response to chemoradiation is imperative for choosing the best surgical option after chemoradiation and predicting the oncologic outcomes of patients. Radiological tools and endoscopy are the most commonly used tools for post-treatment response assessment. In addition, examining the expression levels of genes correlated with treatment response could provide clinicians with more power to gauge each patient’s potential to respond. In this study, we explored how biological and radiological tools can be used together to provide a more tailored and multidimensional representation of patients’ response status.The response to preoperative chemoradiotherapy (PCRT) is correlated with oncologic outcomes in patients with locally advanced rectal cancer. Accurate prediction of PCRT response before surgery can provide crucial information to aid clinicians in further treatment planning. This study aimed to develop an evaluation tool incorporating a genetic biomarker and magnetic resonance imaging (MRI) to improve the assessment of response in post-CRT patients with locally advanced rectal cancer. A total of 198 patients who underwent PCRT followed by surgical resection for locally advanced rectal cancer between 2010 and 2016 were included in this study. Each patient’s response prediction index (RPI) score, a multigene biomarker developed in our previous study, and magnetic resonance tumor regression grade (mrTRG) score were added to create a new predictive value for pathologic response after PCRT, called the combined radiation prediction value (cRPV). Based on the new value, 121 and 77 patients were predicted to be good and poor responders, respectively, showing significantly different cRPV values (p = 0.001). With an overall predictive accuracy of 84.8%, cRPV was superior to mrTRG and RPI for the prediction of pathologic chemoradiotherapy response (mrTRG, 69.2%; RPI, 77.3%). In multivariate analysis, cRPV was found to be the sole predictor of tumor response (odds ratio, 32.211; 95% confidence interval, 14.408–72.011; p = 0.001). With its good predictive value for final pathologic regression, cRPV may be a valuable tool for assessing the response to PCRT before surgery.

Development of a novel apoptosis-based tumor regression grade to assess the efficacy of preoperative chemoradiotherapy for rectal cancer: a retrospective single-center study.

Preoperative chemoradiotherapy is used preferably for locally advanced rectal cancer, followed by a watch-and-wait strategy for cases showing clinical complete response. However, there is a discordance between pathological and clinical complete response rates. We aimed to propose a tumor regression grade (TRG) that truly reflects the therapeutic effects of preoperative chemoradiotherapy in locally advanced rectal cancer. Overall, 293 consecutive patients with T3/T4a/T4b rectal cancer who underwent chemoradiotherapy followed by radical surgery between Sep 2003 and Dec 2018 were retrospectively reviewed. We assessed apoptosis using M30 cytoDEATH immunostaining and correlated that with conventional TRG (convTRG) evaluated using hematoxylin-eosin staining, and created a new TRG by evaluating apoptosis and convTRG. The modified TRG1-4 (modifTRG) classification was as follows: modifTRG1 comprised poor TRG, modifTRG2 moderate TRG, modifTRG3 good TRG, modifTRG4 complete apoptosis and convTRG3 (pathological complete response). We assessed the overall survival, relapse-free survival, and local recurrence rate. Pathological complete response rate was 10.6% when evaluated using conventional staining. Using M30 staining, apoptosis was observed in the residual disease in convTRG 1a 0%, convTRG 1b 0.3%, convTRG 2 9.2%. Combining the two, modifTRG4 was observed in 20.1%. The survival rates were similar between modifTRG4 and convTRG3, suggesting that modifTRG4 was equivalent to pathological complete response. However, in multivariate analysis, modifTRG but not convTRG was an independent risk factor for local and distant recurrences. The proposed modifTRG truly reflected the therapeutic effects of chemoradiotherapy and may be superior to the convTRG to stratify rectal cancer patients treated with chemoradiotherapy.

LincRNA-p21 as predictive response marker for preoperative chemoradiotherapy in rectal cancer.

e15534 Background: Preoperative chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer (RC) patients (pts). Despite the benefits of CRT, its use in non-responder pts can be associated with increased toxicities and resection delay. The identification of CRT response biomarkers, such as long non-coding RNAs (lncRNA), could improve the management of these pts. LincRNA-p21 is a lncRNA involved in the p53 pathway and angiogenesis regulation that acts as prognostic marker in several tumors. We aim to study lincRNA-p21 expression in pretreatment samples from RC pts treated with CRT to evaluate whether lincRNA-p21 can act as a predictive biomarker for CRT response. Methods: RNA from pretreatment endoscopy biopsies from 58 RC pts treated with preoperative CRT at Mutua Terrassa University Hospital were analyzed. Pathological response was classified according to the tumor regression grade (TRG) Dworak classification. LincRNA-p21 expression was determined by RTqPCR and was correlated with CRT response and, time to relapse (TTR), disease-free survival (DFS) and overall survival (OS). Results: Samples from 58 pts were analyzed. Most of them males (n = 40, 69%). Median age at diagnosis of 67 (44-82) years. Fifty (86.2%) pts reported stage III and, 42 (72.4%) pts assessed TRG 0-3 with a 70.7% of downstaging reported. LincRNA-p21 was upregulated in stage III tumors (p &lt; 0.0001) and also in tumors with worst response to CRT regarding TRG, TGR0-3 (TRG0-3, n = 42 vs TRG4, n = 16, p = 0.019). In this line, the ROC curve analysis showed that lincRNA-p21 expression had capacity to distinguish pts with maximum response (TRG4) from others (AUC:0.7; p = 0.02). The binary logistic regression analysis validated its independence as response biomarker. LincRNA-p21 levels correlated with pts relapse after surgery. When the pts were classified in 3 groups, high, medium and low, according to lincRNA-p21 levels, RC pts with highest lincRNA-p21 expression had the shortest TTR. TTR for pts with high levels was 74.5 months (m) (95% CI:31-117), while it was 114 m (95% CI:95-133) for those with Medium levels and 123 m (95% CI:111-134) for those with low levels (p = 0.047). Conclusions: LincRNA-p21 is a marker of advanced disease and worse response to CRT. LincRNA-p21 may add valuable information for individualizing pre-operative CRT in locally advanced RC pts.

Lincp21-RNA as Predictive Response Marker for Preoperative Chemoradiotherapy in Rectal Cancer.

Preoperative chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer (RC) patients, but its use in non-responders can be associated with increased toxicities and resection delay. LincRNA-p21 is a long non-coding RNA involved in the p53 pathway and angiogenesis regulation. We aimed to study whether lincRNA-p21 expression levels can act as a predictive biomarker for neoadjuvant CRT response. We analyzed RNAs from pretreatment biopsies from 70 RC patients treated with preoperative CRT. Pathological response was classified according to the tumor regression grade (TRG) Dworak classification. LincRNA-p21 expression was determined by RTqPCR. The results showed that lincRNA-p21 was upregulated in stage III tumors (p = 0.007) and in tumors with the worst response regarding TRG (p = 0.027) and downstaging (p = 0.016). ROC curve analysis showed that lincRNA-p21 expression had the capacity to distinguish a complete response from others (AUC:0.696; p = 0.014). LincRNA-p21 was shown as an independent marker of preoperative CRT response (p = 0.047) and for time to relapse (TTR) (p = 0.048). In conclusion, lincRNA-p21 is a marker of advanced disease, worse response to neoadjuvant CRT, and shorter TTR in locally advanced RC patients. The study of lincRNA-p21 may be of value in the individualization of pre-operative CRT in RC.

Evaluation of a multiparametric MRI scoring system for histopathologic treatment response following preoperative chemoradiotherapy for rectal cancer

PurposeTo evaluate the performance of a multiparametric (mp) MRI scoring system for assessment of tumour response in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (CRT). MethodFifty-nine consecutive patients with LARC who had rectal MRI before and after CRT followed by surgery were included. Two radiologists retrospectively assessed tumour response using a proposed mpMRI scoring system. Treatment response was classified as complete, near complete, partial or poor. Accuracy, sensitivity, specificity, positive predictive value and negative predictive values were calculated and inter-reader agreements were assessed. Pathologic tumour regression grade (pTRG) was the reference standard. ResultsTreatment response was correctly predicted by both readers in 32.2%–40.7% of patients. Overestimation was more common than underestimation. Sensitivity, specificity, PPV and NPV for pathologic complete response (pCR) among both readers was 16.7–33.0 %, 88.7–94.2 %, 14.3–40.0 % and 92.5–94.2 % respectively. Sensitivity and PPV for both readers improved to 56.0–60.0 % and 53.6–66.7 % respectively when complete response and near complete response categories (good responders) were combined. Inter-reader agreement using the scoring system was fair (κ = 0.383). Agreement between mpMRI score and pathological tumour response was poor to fair for both readers (κ = 0.050 to 0.258) but improved when complete and near complete response categories (good responders) were combined (κ = 0.214 to 0.362). ConclusionsDespite low agreement between radiological tumour response and pTRG, the proposed mpMRI-based scoring system appears useful in identifying good responders who may benefit from nonoperative management strategies.

Effect of anaemia on the response to preoperative chemoradiotherapy for rectal cancer.

Radiation therapy with concurrent chemotherapy is an important treatment for rectal cancer, especially for advanced stage disease. Low serum haemoglobin levels are accepted as a negative indicator in the response to radiation therapy. This study aimed to evaluate the relationship between anaemia and the response to preoperative chemoradiotherapy for rectal cancer and its effect on oncologic outcomes. We retrospectively reviewed medical records of primary rectal cancer patients who were treated with preoperative chemoradiotherapy followed by total mesorectal excision between January 2011 and December 2015. Anaemia was defined as serum haemoglobin levels ≤9g/dL before or during radiotherapy. Patients were divided into good and poor responders according to pathologic tumour regression grades. The effect of anaemia on the response to radiation therapy, recurrence-free survival and overall survival were analysed after subgroup analysis. Overall, 301 and 394 patients were categorized into good and poor responder groups, respectively. Proportions of anaemia patients were higher in the poor responder group than in the good responder group (7.6% versus 4.0%, P=0.042). Anaemia was associated with less pathologic complete regression but was not a risk factor for worse recurrence-free or overall survival. There was no significant difference in survival between patients with and without anaemia. Haemoglobin levels ≤9g/dL before or during radiotherapy were risk factors for achieving pathologic complete regression after preoperative chemoradiotherapy for rectal cancer. However, anaemia was not independently associated with worse survival outcomes.

PD-0534: Dose-escalation phase III trial of preoperative chemoradiotherapy in rectal cancer. First results

PD-0534: Dose-escalation phase III trial of preoperative chemoradiotherapy in rectal cancer. First results

Signet ring cell component in pretreatment biopsy predicts pathological response to preoperative chemoradiotherapy in rectal cancer.

Neoadjuvant therapy is routinely used in the management of locally advanced rectal cancer. This study aimed to evaluate the predictive value of pathological parameters in tumor response after treatment. We reviewed the hematoxylin-eosin slides from pretreatment biopsies of 150 rectal cancer patients who received preoperative chemoradiotherapy (PCRT) at Sun Yat-sen University Cancer Center between May 2013 and June 2016. Pathological and clinical parameters were both studied. The tumor response after chemoradiotherapy was evaluated using the tumor regression grade (TRG). Logistic regression was used to evaluate the relevance between these parameters and tumor response. Complete tumor response (TRG0 and pCR) to PCRT was identified in 40 (26.7%) patients. The pCR rate was 93.33% (14 of 15) in cases with signet ring cell component versus 19.26% (26 of 135) in those without signet ring cell component (p < 0.001). Four cases with signet ring cell component were evaluated as clinical complete response (cCR), all of whom also achieved pCR; in contrast, only 9 of 15 (60%) cCR cases without signet ring cell achieved pCR. Our data suggest that the signet ring cell component in pretreatment biopsies may be a potential predictor of tumor response to PCRT in rectal cancer. This suggests patients with clinical complete response are more suitable for a wait-and-watch approach.

Importance of the neoadjuvant rectal (NAR) score to the outcome of neoadjuvant chemotherapy alone for locally advanced rectal cancer.

The neoadjuvant rectal (NAR) score is a promising indicator of survival after preoperative chemoradiotherapy for rectal cancer. However, its effectiveness after neoadjuvant chemotherapy (NAC) alone has not been fully investigated. We analyzed data retrospectively on 61 patients with rectal cancer, who received NAC followed by surgical resection between 2010 and 2015, and evaluated the impact of the NAR score on survival. The median NAR score was 14.9. Of the 61 patients, 13, 35, and 13 were classified as having NAR-low (< 8), NAR-intermediate (8-16), and NAR-high (> 16) scores, respectively. The median observation period was 49.0months. According to the NAR score, the 3-year DFS in the NAR-low group was 100%, which was significantly better than that in the NAR-intermediate (64.8%, p = 0.041), and NAR-high (61.5%, p = 0.018) groups. When the NAR-intermediate and NAR-high groups were investigated as a single high-risk group, the 3-year DFS of the patients who received adjuvant chemotherapy was 88.7%, which was significantly better than that of the patients who did not receive adjuvant chemotherapy (53.3%, p = 0.042). The NAR score may predict the DFS and could serve as a favorable indicator of adjuvant chemotherapy after NAC alone.

Predictive value of serum and tissue carcinoembryonic antigens for radiologic response and oncologic outcome of rectal cancer

PurposeThe clinical importance of tissue CEA levels for predicting tumor response to preoperative chemoradiotherapy (CRT) for rectal cancer has not been studied. MethodsSerum CEA levels and tissue CEA expressions for 117 patients who underwent preoperative CRT for rectal cancer, were prospectively collected and analyzed at a tertiary university hospital ResultsThe median follow-up time was 49 months (range, 3–61 months), and the 5-year disease-free survival (DFS) rate was 68.3 %. In multivariate analysis, serum CEA (log-transformed value) [odds ratio (OR) = 0.741, 95 % confidence interval (CI) 1.588–40.422, P = 0.021], tissue CEA/GAPDH ratio (OR = 3.673, 95 % CI 1.316–12.081, P = 0.019), and tumor circumferentiality (OR = 2.960, 955 CI, 1.101–8.999, P = 0.040) were the independent predictors for good tumor response to CRT. Serum CEA level was significant prognostic factor for DFS (P = 0.004) in multivariate analysis. However, tissue CEA was not associated with DFS. ConclusionsBoth serum and tissue CEA were significant factors for predicting good tumor response following preoperative CRT. However, tissue CEA was not associated with the oncologic outcome. The possibility of radiologic resistance of high CEA tumors is expected to be investigated through further studies.

Nomogram for prediction of pathologic complete remission using biomarker expression and endoscopic finding after preoperative chemoradiotherapy in rectal cancer.

ObjectiveThe aim of this study is to develop a nomogram for prediction of pathologic complete remission (pCR) after preoperative chemoradiotherapy (CRT) for rectal cancer.MethodsmRNA expression levels of seven molecular markers [p53, p21, Ki-67, vascular endothelial growth factor (VEGF), CD133, CD24, CD44] were measured by reverse transcriptase polymerase chain reaction (RT-PCR) in 120 rectal cancers. Endoscopic findings of clinical complete remission (cCR) and biologic variables were used to construct nomogram in the training group (n=80), which was validated in the validation group (n=40).ResultsmRNA expression levels of four markers (p53, p21, Ki67, CD133) correlated with pCR (24/80, 30.0%) in the training group. Low expression of p53 and/or high expression of p21, Ki67 and CD133 showed greater pCR rate. pCR was shown in 18 (69.2%) of 26 cases showing endoscopic cCR in the training group. Higher pCR rate was demonstrated in lower tumor location than middle tumor (19/49, 38.8% vs. 5/31, 16.1%). A nomogram for prediction of pCR was developed from the multivariate prediction model using these six variables, which showed good discrimination ability in the training group [area under the curve (AUC)=0.945] and validation group (AUC=0.922). The calibration plot showed good agreement between actual and predicted pCR in both patient groups. ConclusionsNomogram for assessment of pCR can be useful for making treatment decisions after CRT according to predicted responses.

FT3-L Dynamics in Blood Could be Predictive of Time of Occurrence Lymphocyte Nadir in Patients Undergoing Preoperative Chemoradiotherapy for Rectal Cancer.

The Fms-like tyrosine kinase 3 receptor (Flt-3) in conjunction with Flt-3 ligand (Flt-3L) participate in the growth and survival of bone marrow (BM) progenitor cells. To the best of our knowledge, correlation between concentration of Flt-3L in patients’ blood during 3-D planned chemoradiotherapy (CRT) and nadirs of lymphocytes (ALCnadir), neutrocytes (ANCnadir), platelets (PLTnadir), red blood cells (RBCnadir) has not been assessed yet. Available data comes from preclinical studies and small clinical studied without evaluation of dose-volume parameters of BM. Our pilot study aims to access clinical utility of Flt-3L concentration in patients’ blood during CRT. 33 patients qualified to preoperative CRT were enrolled. Blood samples for Flt-3L were collected at baseline, at 2nd, 4thand 5/6thweek; for ALC, ANC, PLT, and RBC every week. Flt-3L variability was assessed over time using Friedman’s ANOVA. The model for prediction of ALC, ANC, PLT, RBC nadir week was developed. The Flt-3L measured levels as well as relative changes between following weeks were used for decision tree induction using C4.5 algorithm. Resulting modelling method of prediction was assessed for overfitting in leave-one-out cross-validation. The concentration of Flt-3L was statistically significantly higher than the initial value from the second week of chemo-radiotherapy (in 2nd, 4thand 5/6thweek of CRT). Final model presented the accuracy of 84.8% and utilized the relative change of Flt-3L between baseline and 2ndweek, 2ndand 4thweek and the measurement at 5/6thweek. Weighted average area under the ROC curve in validation on training set for all weeks was 0.91. The accuracy in leave-one-out cross-validation was estimated as 69.7%. This pilot study presents the potential of Flt-3L in prediction of week of occurrence of lymphocyte nadir during preoperative CRT of rectal cancer. Further studies with larger number of participants could provide an overfitting-resistant and clinically applicable model for prediction of the expected week at which lymphocyte nadir occurs, hence enhance treatment monitoring. Additionally, in our complementary study ALC nadir was connected with dose-volume parameters of bone marrow, what may add clinical significance.

A Multigene Model for Predicting Tumor Responsiveness After Preoperative Chemoradiotherapy for Rectal Cancer

Although preoperative chemoradiotherapy (PCRT) is regarded as a standard treatment for locally advanced rectal cancer, there is no reliable biomarker for predicting responsiveness to PCRT. We aimed to develop a biomarker model for predicting response to PCRT. We included 184 patients who received PCRT followed by surgical resection and categorized them as good responders (complete or near-complete regression) or poor responders (all other patients). Candidate gene mRNAs were isolated from formalin-fixed paraffin-embedded tumor specimens and analyzed using the NanoString nCounter gene expression assay. Stepwise logistic regression analysis was used to select genes in discovery and training phases. A quantitative radio-responsiveness prediction model was developed and validated using internal cross-validation groups, and the model's predictive value was assessed based on the area under the receiver operating characteristic curve (AUC). By comparing the gene expressions between good and poor responders, we created a multigene mRNA model using FZD9, HRAS, ITGA7, MECOM, MMP3, NKD1, PIK3CD, and PRKCB. This panel showed good ability to predict treatment response (AUC: 0.846 for the whole data set). Internal cross-validation was performed to evaluate the model's predictive stability among 3 cohorts, which provided AUC values of 0.808-0.909. The satisfactory diagnostic performance of the radio-response prediction index persisted regardless of other clinicopathologic features such as clinical T or N stage, interval between radiation and surgery, and pretreatment carcinoembryonic antigen levels (P = .001, 95% CI, 0.686-0.905). We developed a multigene mRNA-based biomarker model that allows prediction of rectal cancer response to PCRT, which may help identify patients who will benefit most from PCRT.